Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex
Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex–protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-Hi...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/81172 http://hdl.handle.net/10220/39145 |
| _version_ | 1826122913056555008 |
|---|---|
| author | Heddi, Brahim Cheong, Vee Vee Martadinata, Herry Phan, Anh Tuân |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Heddi, Brahim Cheong, Vee Vee Martadinata, Herry Phan, Anh Tuân |
| author_sort | Heddi, Brahim |
| collection | NTU |
| description | Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex–protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures. |
| first_indexed | 2024-10-01T05:56:02Z |
| format | Journal Article |
| id | ntu-10356/81172 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:56:02Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/811722023-02-28T19:30:11Z Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex Heddi, Brahim Cheong, Vee Vee Martadinata, Herry Phan, Anh Tuân School of Physical and Mathematical Sciences G-quadruplex DHX36 DEAH-box family NMR RHAU helicase Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex–protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures. MOE (Min. of Education, S’pore) Accepted Version 2015-12-17T08:49:32Z 2019-12-06T14:22:57Z 2015-12-17T08:49:32Z 2019-12-06T14:22:57Z 2015 Journal Article Heddi, B., Cheong, V. V., Martadinata, H., & Phan, A. T. (2015). Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex. Proceedings of the National Academy of Sciences of the United States of America, 112(31), 9608-9613. https://hdl.handle.net/10356/81172 http://hdl.handle.net/10220/39145 10.1073/pnas.1422605112 26195789 en Proceedings of the National Academy of Sciences of the United States of America © 2015 The Author(s) (Published by National Academy of Sciences). This is the author created version of a work that has been peer reviewed and accepted for publication by Proceedings of the National Academy of Sciences of the United States of America, The Author(s) (Published by National Academy of Sciences). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1073/pnas.1422605112]. 6 p. application/pdf |
| spellingShingle | G-quadruplex DHX36 DEAH-box family NMR RHAU helicase Heddi, Brahim Cheong, Vee Vee Martadinata, Herry Phan, Anh Tuân Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex |
| title | Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex |
| title_full | Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex |
| title_fullStr | Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex |
| title_full_unstemmed | Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex |
| title_short | Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex |
| title_sort | insights into g quadruplex specific recognition by the deah box helicase rhau solution structure of a peptide quadruplex complex |
| topic | G-quadruplex DHX36 DEAH-box family NMR RHAU helicase |
| url | https://hdl.handle.net/10356/81172 http://hdl.handle.net/10220/39145 |
| work_keys_str_mv | AT heddibrahim insightsintogquadruplexspecificrecognitionbythedeahboxhelicaserhausolutionstructureofapeptidequadruplexcomplex AT cheongveevee insightsintogquadruplexspecificrecognitionbythedeahboxhelicaserhausolutionstructureofapeptidequadruplexcomplex AT martadinataherry insightsintogquadruplexspecificrecognitionbythedeahboxhelicaserhausolutionstructureofapeptidequadruplexcomplex AT phananhtuan insightsintogquadruplexspecificrecognitionbythedeahboxhelicaserhausolutionstructureofapeptidequadruplexcomplex |